COmbiNed eFfIcacy and safety of an eaRly, intensive MAnagement sTrategy with fInerenOne and SGLT2 iNhibitor in patients hospitalized with Heart Failure(CONFIRMATION-HF)
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 125
- 试验地点
- 8
- 主要终点
- 1. Time to all cause mortality
研究概览
简要总结
This is a Phase 3 randomized, controlled, open label study which compares two management strategies in patients with an acute episode of decompensated HF: an early, intensive strategy of finerenone initiated simultaneously with a sodium-glucose co-transporter inhibitor (SGLT2i) versus standard of care.
Since Finerenone has demonstrated to reduce the risk of sustained estimated glomerular filtration rate decline, end stage kidney disease, cardiovascular death, non-fatal myocardial infarction, and hospitalization for heart failure in patients with chronic kidney disease associated with type 2 diabetes, it’s combination with SGLT2i class of drugs -which are also recommended to reduced HF hospitalization and CV mortality in patients with HFrEF with or without diabetes and have been shown to lower the combined risk of worsening HF or CV death in patients with HF. Hence establishing that early initiation of combination therapy with finerenone and SGLT2i is well tolerated and can improve clinical outcomes that could have a practice changing impact.
Patients will be screened based on the inclusion/exclusion criteria and will be randomly allocated (1:1) to standard of care management or an early, intensive management strategy including empagliflozin 10 mg daily and finerenone once daily at a starting dose of 10 or 20 or 40 mg based on their local laboratory eGFR at baseline.
Outcome will be assessed based on the Primary objective: whether a strategy of early, intensive combination therapy with finerenone and empagliflozin provides superior clinical outcomes compared with local standard of care in patients with HHF., Secondary objective: whether early, intensive combination therapy can reduce all-cause mortality and total HF events (first and recurrent), improve KCCQ-TSS (at 6 months) and reduce HF events (at 90 days) and the Safety objective: by assessing the occurrence of AEs with finerenone and empagliflozin compared with standard of care.
The analysis of the endpoints will be performed as per the Statistical Analysis Plan and Safety Analysis Set.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 盲法
- Participant, Investigator and Outcome Assessor Blinded
入排标准
- 年龄范围
- 18.00 Year(s) 至 99.00 Year(s)（—）
- 性别
- All
入选标准
- •Provide electronic or written informed consent , either personally or through a legally authorized representative (LAR) as permitted by local regulations.
- •Age greater than or equal to 18 years or legal age of majority if greater than 18 years in the participants country of residence.
- •Current hospitalization or recently discharged (within 10 days prior to screening) with the primary diagnosis of HF.
- •Heart failure signs and symptoms at the time of hospital admission, including a.Symptoms (at least one of the following) persistent dyspnea at rest or with minimal exertion worse than baseline or new or worsening orthopnea, and b.Signs of fluid overload (at least one of the following) congestion on chest X-ray, rales on chest auscultation, clinically relevant edema caused by HF (as judged by the investigator), elevated jugular venous pressure 5.Elevated N terminal pro B type natriuretic peptide (NTproBNP) greater than or equal to 500 pg per mL or Btype natriuretic peptide (BNP) greater than or equal to 125 pg per mL according to the local lab for patients in sinus rhythm or elevated NTproBNP greater than or equal to 1500 pg per mL or BNP greater than 375 pg per mL for patients with atrial fibrillation (AF), measured during the current hospitalization or in the 72 hours prior to hospital admission.
- •(Note for patients treated with an angiotensin receptor neprilysin inhibitor [ARNI] in the previous 4 weeks prior to randomization, only NTproBNP values should be used.) 6.Fulfillment of the following stabilization criteria (if randomized during hospitalization) a.Systolic BP greater than or equal to 100 mmHg and no symptoms of hypotension in the 6 hours prior to randomization.
- •b.No increase in intravenous diuretic dose for 6 hours prior to randomization.
- •c.No intravenous vasodilators, including nitrates, within the last 6 hours prior to randomization.
- •d.No intravenous inotropic drugs or mechanical circulatory support for 24 hours prior to randomization 7.Treatment during the index hospitalization with at least 1 intravenous dose of a loop diuretic (eg furosemide, torsemide, bumetanide).
- •8.Women of childbearing potential can only be included in the study if a pregnancy test is negative at screening and if they agree to use adequate contraception which is consistent with local regulations regarding the methods for contraception for the duration of the study.
排除标准
- •1.Diagnosis of type 1 diabetes or prior history of diabetic ketoacidosis.
- •2.Documented prior history of severe hyperkalemia (potassium greater than or equal to 6.0 mmol per L and/or resulting in hospitalization or Emergency Department visit) in the setting of MRA use.
- •3.Treatment with non steroidal MRA (finerenone, esaxerenone, apararenone), steroidal MRA (spironolactone, eplerenone, canrenone), or SGLT2i within 30 days prior to randomization treatment with steroidal or non-steroidal MRA or SGLT2i should not be interrupted for the purpose of enrollment into the study.
- •4.eGFR less than 30 mL per min per 1.73m square and or potassium less than 5.0 mmol per L at screening.
- •5.Acute MI, coronary revascularization, valve replacement or repair, or implantation of a cardiac resynchronization therapy device within 30 days prior to randomization.
- •(Note pacemakers or implantable cardioverter defibrillators without resynchronization function are allowed.) 6.Prior heart transplant or listed for heart transplant with expectation to receive a transplant during the course of this trial (according to investigator judgement) or currently using or plan for mechanical circulatory support eg left ventricular assist device, intra-aortic balloon pump, or patients on mechanical ventilation or patients with planned outpatient inotropic support.
- •7.Hemodynamically significant (severe) uncorrected primary cardiac valvular disease considered by the investigator to be the primary cause of HF.
- •(Note secondary mitral regurgitation or tricuspid regurgitation due to dilated cardiomyopathy is not excluded unless planned for surgery or intervention during the course of the study.) 8.Cardiomyopathy due to known acute inflammatory heart disease (eg acute myocarditis within 90 days prior to randomization), infiltrative diseases (eg amyloidosis), accumulation diseases (eg haemochromatosis, Fabry disease), muscular dystrophies, cardiomyopathy with reversible causes (eg stress cardiomyopathy), known hypertrophic obstructive cardiomyopathy, complex (according to investigator s judgement) congenital heart disease, or known pericardial constriction.
- •9.Probable alternative cause of participant s HF symptoms that, in the opinion of the investigator, primarily accounts for patient s symptoms specifically, patients with severe pulmonary disease requiring home oxygen or chronic oral steroid therapy, primary pulmonary arterial hypertension at screening.
- •10.Concomitant systemic therapy with potent cytochrome P450 isoenzyme 3A4 (CYP3A4) inhibitors (eg itraconazole, ritonavir, indinavir, cobicistat, clarithromycin), or moderate CYP3A4 inducers (eg efavirenz, phenobarbital), or potent CYP3A4 inducers (eg carbamazepine, phenytoin, St. John s Wort) that cannot be discontinued 7 days prior to randomization and for the duration of the treatment period.
- •11.Known hypersensitivity to the IP (active substance or excipients).
- •12.Any other condition or therapy (eg breastfeeding, cardiogenic shock, clinically overt severe hepatic insufficiency [Child Pugh C], Addison s disease, or other severe condition as per investigator s judgment such as disease with less than 1 year life expectancy) which would make the participant unsuitable for this study and not allow participation for the full planned study period.
- •13.Concurrent participation in another interventional clinical study using an investigational agent (eg not approved for any indication) within 30 days prior to randomization.
结局指标
主要结局
1. Time to all cause mortality
时间窗: Ongoing, up to 18 months
2. Number of total HF events (first and recurrent hospitalization or urgent outpatient visit for HF)
时间窗: Ongoing, up to 18 months
3. Time to first HF event
时间窗: Ongoing, up to 18 months
4. Kansas City Cardiomyopathy Questionnaire-Total Symptom Score (KCCQ-TSS) change from baseline to 6 months of 5 points or greater assessed by the win-ratio method.
时间窗: Ongoing, up to 18 months
5. Serious Adverse events
时间窗: Ongoing, up to 18 months
6. Adverse events leading to discontinuation of IP.
时间窗: Ongoing, up to 18 months
次要结局
- KCCQ-TSS, mean change from baseline to 6 months
- Time to first occurrence of all-cause mortality or HF event (hospitalization for HF or urgent visit due to HF)(Ongoing, up to 18 months)
- Total (first and recurrent) HF events from baseline to 90 days(90 days)
研究者
Dr Vijay Kumar Chopra
Max Super Speciality Hospital